Chronic fatigue syndrome (CFS) is a disease which has been present in human populations for a very long time. However, only recently have we begun to investigate its clinical and laboratory diagnostic features. At present, while there is a reasonable well-defined set of clinical signs characteristic of CFS, collection of values remains to be established which might be used to make a firm laboratory diagnosis. In addition, we presently have no clear ideas on the cause of CFS, either on its initiation or on the basis for its chronic nature. We propose to examine a cohort of CFS patients, diagnosed on clinical as well as on laboratory criteria, in conjunction with three sets of appropriate control populations. Our examination will be on a broad basis, involving a number of immunological assays. In particular, we will use a novel PCR-based quantitative assay which we have developed in our laboratory for the analysis of cytokine gene expression. This assay is particularly useful since it can detect changes in cytokines levels that may have marked effects physiologically but are difficult to detect using more conventional methods, such as measurement of serum cytokine levels. Because functions for many of the cytokines are known, alterations in cytokine production may provide considerable insight into the etiology of immune dysfunction and the effects on other physiological systems. In addition, on the basis of these data, we will test interactions in vitro between cytokines(s) and virus(es) which may be relevant to the appearance of CFS symptoms in patients.